While there is much in flux about Gus Van Sant’s upcoming adaptation of Tom Wolfe’s Zeitgeist-defining book, “The Electric Kool-Aid Acid Test,” which centers on the LSD-infused cross-country road trip that novelist Ken Kesey and his Merry Pranksters took in the 1960s, the director is certain about one thing: he won’t be able to cast his ideal leading man.

“Unfortunately, Heath Ledger was a pretty obvious choice, and he’s gone,” Van Sant told MTV News in an exclusive interview. But who else could play zany philosopher-king and “One Flew Over The Cuckoo's Nest” author Kesey?

“There’s the opportunity that it could be Jack Black,” says Van Sant, hinting the film might possibly take on a more comedic feel.

At the moment, though, the “Milk” director is awaiting the initial draft of the screenplay, which is being penned by “Milk” scriptwriter Dustin Lance Black.

“He’s cracking the nut,” Van Sant tells us. “I’m not sitting with him every day. I probably should think about doing that, but I haven’t seen the first draft yet. I hope he cracks it. There are many ways to crack it.”

Indeed, Wolfe’s “Electric Kool-Aid Acid Test” is a sprawling, multi-storyline beast of narrative nonfiction following, among other things, the LSD “test” parties Kesey and the Pranksters staged in San Francisco; early Grateful Dead shows; the Hells Angels biker gang; the psychedelic bus called "Further" that Kesey’s wacked-out crew drove across the country, making experimental films and tripping their faces off; the drug-related legal troubles Kesey eventually encountered; and, of course, the wild, wild experience of dropping acid in Haight-Ashbury before the rest of America began to turn on, tune in and drop out.

However the finished script turns out, what is clear is the source material is dear to Van Sant’s heart. He cast Kesey in his 1993 film "Even Cowgirls Get the Blues" and dedicated 2002’s “Gerry” to the memory of the author, who died from complications following surgery for liver cancer in 2001. And for “Acid Test,” when it comes time to cast the leading man after Sean Penn blew critics away with his turn as Harvey Milk, the Kesey role as directed by Van Sant will surely be chased by almost every able-bodied actor in Hollywood.

What do you think of the potential casting choices? Who should play Ken Kesey? What about Jerry Garcia?